Our major objectives in the next year are to better define the role natural killer (NK) cells play in autoimmune disease and to develop new monoclonal antibodies (MAb) which define NK cell subsets in mouse and man. The cellular basis of the beige gene-controlled lupus-like autoimmune disease of SB/Le mice will be investigated using in vitro functional assays, quantitative two-color cytofluorimetry, cell sorting, and adoptive transfers of distinct cell subsets. MAb will be developed to alloantigens expressed in "NK high" A.SM congenic mice not expressed in "NK low" A parental mice. The biochemical nature and gene control of these antigens will be studied. Using a large panel of MAb reactive with nonhuman primate WK, T, and B lymphoid cell subsets and two-color immunofluorescence, we will monitor NK cell subsets changes during the development and resolution of subacute autoimmune encephalitis. As MAb and NK subsets are identified in these two autoimmune disease models, the effect on disease of specific immunotherapy to remove NK cells will be assessed. (SR)